Galectin-1 ameliorates perioperative neurocognitive disorders in aged mice

2020 ◽  
Author(s):  
Yi Wu ◽  
Wen Song ◽  
Zhiwen Shen ◽  
Yaowei Zhi ◽  
Guiyun Wu ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Exploratory Laparotomy ◽  
The Elderly ◽  
Neurocognitive Disorders ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aged Mice ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Bv2 Microglial Cells

Abstract Background The incidence of perioperative neurocognitive disorders (PND) is higher in the elderly patients undergoing surgery. Microglia activation-mediated neuroinflammation is one of the hallmarks of PND. Galectin-1 has been identified as pivotal modulator in central nervous system (CNS), while the role of galectin-1 in PND induced by microglia-mediated neuroinflammation is still undetermined. Methods An exploratory laparotomy model anesthetized with isoflurane was employed to investigate the role of galectin-1 on PND in aged mice. Open field test and Morris water maze were used to test the cognitive function 3 or 7 days after surgery. Immunofluorescence staining was employed to detect the activation of microglia and neuronal integrity in the hippocampus of aged mice. Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to elucidate the underlying mechanisms. Results Pretreatment with galectin-1 attenuated the cognitive dysfunction induced by surgery in aged mice and inhibited microglial activity. Moreover, galectin-1 decreased the expression level of inflammatory proteins (interleukin-1β, interleukin-6 and tumor necrosis factor-α), and disrupted neuronal integrity in hippocampus. Galectin-1 inhibited the inflammation of BV2 microglial cells induced by lipopolysaccharide via decreasing the translocation of c-Jun and NF-κB p65, while this kind of inhibition was rescued when overexpressing IRAK1. Conclusions Our findings provide evidence that galectin-1 may inhibit IRAK1 expression, thus suppressing inflammatory response, inhibiting neuroinflammation, and improving ensuing cognitive dysfunction. Collectively, these findings unveil that galectin-1 may elicit protective effect on surgery-induced neuroinflammation and neurocognitive disorders.

scholarly journals The Expression of Interleukin-1β Is Regulated by DNA Methylation in Microglia of Hippocampus to Participate Postoperative Cognitive Dysfunction in Aged Mice

2021 ◽  
Author(s):  
Yin Gao ◽  
Li Yang ◽  
Xiu Yang ◽  
Jing-Ru Hao ◽  
Xiao-Ran Shen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Synaptic Plasticity ◽  
Cognitive Dysfunction ◽  
Western Blotting ◽  
Dorsal Hippocampus ◽  
The Elderly ◽  
Aged Mice ◽  
Promoter Dna Methylation ◽  
Promoter Dna

Abstract BackgroundPostoperative cognitive dysfunction (POCD) is one of the common postoperative complications in the elderly. The main clinical manifestation is memory impairment, which can cause permanent damage and even dementia in severe cases. However, the pathogenesis of POCD is still unknown. Age and neuroinflammation are known to be closely related to its occurrence, while DNA methylation is very important for transcriptional silencing and neuroinflammation. Consequently, this study intended to establish a mouse model of POCD to explore the role of DNA methylation in regulating the expression of interleukin-1β which participated POCD in aged mice.MethodsPOCD model was established by exploratory laparotomy and evaluated by new object experiment and Y maze test. In addition, ELISA, RT-PCR, Western blotting, immunofluorescence, microglia isolation and flow cytometry methods were used to detect the inflammatory state of dorsal hippocampal after surgery. Moreover, MSP, MeDIP and IL-1β promoter DNA methylation sequencing were used to explore the regulation of DNA methylation on IL-1β in this model. Finally, Golgi staining and Western blotting were used to further explore the role of IL-1β in POCD and its possible mechanisms. ResultsCognitive impairment was observed in aged but not adult mice at 1 day after surgery. There was a significant correlation between the level of IL-1β in dorsal hippocampus and the performance of cognitive function. The microglia in the dorsal hippocampus was activated and the IL-1β promoter DNA methylation was decreased in the aged mice. The increased expression of IL-1β impaired synaptic plasticity and hippocampus-dependent memory formation. Intracerebroventricular administration of IL-1β receptor antagonist could prevent the cognitive impairment of aged mice after surgery, reverse the decrease of dendritic spine density and synapse-associated protein expression induced by surgery.ConclusionDNA methylation regulation may be an important mechanism for greater susceptibility to POCD in aged mice by regulating the expression of IL-1β. IL-1β inhibiting prevented surgery-induced cognitive decline and synaptic plasticity dysfunction. The research also provided a new target for the clinical prevention of the occurrence of POCD in the elderly.

Abstract 65: Restoration of Growth Differentiation Factor 11 Protects Against Stroke in Mice

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Anjali Chauhan ◽  
Jacob Hudobenko ◽  
Anthony Patrizz ◽  
Louise D McCullough
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
The Elderly ◽  
Vehicle Group ◽  
Peripheral Tissues ◽  
Delayed Treatment ◽  
Aged Mice ◽  
Infarct Area ◽  
Age Related

Introduction: GDF 11 is a member of the transforming growth factor β superfamily. Loss of GDF11 occurs with aging and declining levels correlate with several detrimental age-associated phenotypes in both peripheral tissues and brain. Restoration of GDF11 enhances neurogenesis and cognitive function in aged mice. Brain expression of GDF11 has not been investigated after stroke. Stroke differentially affects the elderly. In this work we examined the role of GDF11 in aging, stroke and its potential utility as a neuroprotective agent. Methods: Male C57/BL6NCrl young (2-3 months) and aged (19-21) mice were used. Brain GDF11 expression was evaluated in young and aged mice by western blot. Focal ischemia was induced with a transient middle cerebral artery occlusion (MCAO). Mice were randomly assigned into two groups and were subjected to 90 min MCAO. Group 1 received vehicle (phosphate buffered saline) and group 2 was administered rGDF11 (100 ug/kg., ip) at the onset of ischemia. In additional experiments, the efficacy of delayed treatment (3 h after ischemia) with rGDF11 was tested. These mice were subjected to a 60 min MCAO. Mice were euthanized after 24 hours and 7 days respectively and brains were harvested to estimate infarct area. Results: A significant decrease in brain GDF11 levels was observed in aged mice as compared to young (p<0.05). Additionally, a significant decline in brain GDF11 expression was observed after stroke at 24 hours vs. sham groups (p<0.05). A significant decrease in cortical and hemispheric infarct area was observed in the rGDF11 group (cortical 48.73±1.05; hemisphere 49.68±3.58) as compared to vehicle group (60.54±4.88; 61.35±6.03), when GDF was administered at the time of ischemia. Delayed treatment with rGDF11 also reduced infarct at 7 days. Conclusions: Brain GDF11 levels decline with age and after stroke. Supplementation with rGDF11 ameliorates stroke induced injury in young mice at 24h and 7 days. These finding suggest potential role of GDF11 in age and stroke. Restoration of age-related loss of GDF may be a viable therapy for stroke.

scholarly journals Carotenoids: How Effective Are They to Prevent Age-Related Diseases?

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1801 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan
Keyword(s):  
Oxidative Stress ◽  
Healthy Aging ◽  
The Elderly ◽  
Antioxidant Systems ◽  
Potential Intervention ◽  
Healthy Longevity ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Endogenous Antioxidant

Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.

Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 4011-4018 ◽  
Author(s):  
Koji Yamamoto ◽  
Takayoshi Shimokawa ◽  
Hong Yi ◽  
Ken-ichi Isobe ◽  
Tetsuhito Kojima ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Restraint Stress ◽  
Vascular Endothelial Cells ◽  
Obese Mice ◽  
Adipose Tissues ◽  
Aged Mice ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Tf Gene ◽  
Factor Α

Hypercoagulability and thrombotic tendency are frequently induced by a variety of stressors. Clinically, aged subjects and obese patients are more susceptible to thrombotic diseases associated with stress, but the underlying mechanisms are unknown. We investigated the expression of a procoagulant gene, tissue factor (TF), in a mouse model of restraint stress. Twenty hours of restraint stress to mice caused a substantial induction of TF mRNA in several tissues. Importantly, the magnitude of induction of TF mRNA by restraint stress was larger in aged mice compared with young mice. In situ hybridization analysis of the stressed aged mice revealed that strong signals for TF mRNA were localized to renal epithelial cells, smooth muscle cells, adventitial cells, and adipocytes but not to vascular endothelial cells. These observations suggest that restraint stress induces the TF expression in a tissue-specific and cell type–specific manner. Genetically obese mice were also hyperresponsive to restraint stress in the induction of TF gene, especially in their livers and adipose tissues. Stress-induced microthrombi formation was pronounced in renal glomeruli and within the vasculature in adipose tissues of aged mice. Tumor necrosis factor-α (TNF-α) antigen in plasma was elevated by stress in aged mice and obese mice, and pretreatment of mice with anti–TNF-α antibody partially attenuated the stress-mediated induction of TF gene in adipose tissues in these mice. These results suggest that the induction of TF gene may increase the risk of stress-associated thrombosis in older and obese subjects and that TNF-α may be involved.

scholarly journals A Dysregulated MicroRNA-26a/EphA2 Axis Impairs Endothelial Progenitor Cell Function via the p38 MAPK/VEGF Pathway

2015 ◽  
Vol 35 (2) ◽  
pp. 477-488 ◽  
Author(s):  
Keqiang Zuo ◽  
Kangkang Zhi ◽  
Xiaoping Zhang ◽  
Chenghui Lu ◽  
Shi Wang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Cell Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Endothelial Progenitor ◽  
Circulating Micrornas ◽  
Circulating Endothelial Progenitor Cells ◽  
Novel Biomarkers ◽  
Vegf Pathway ◽  
Underlying Mechanisms

Background: Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms. Methods: EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a. Results: MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs. Conclusions: The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.

Anti-inflammatory role of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) in nephroprotection

2019 ◽  
Vol 38 (6) ◽  
pp. 713-723 ◽  
Author(s):  
MA Afjal ◽  
SA Hasan Abdi ◽  
S Sharma ◽  
S Ahmad ◽  
M Fatima ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Immunohistochemical Analysis ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Important Evidence ◽  
Necrosis Factor

Inflammation is one of the mechanisms involved in the acute kidney injury (AKI) caused by cisplatin (CP)-induced nephrotoxicity. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) has powerful antioxidant activity. We investigated its potential nephroprotective effects and the underlying mechanisms that may add further benefits to its clinical usefulness in a CP-induced AKI model. Male Swiss albino mice were divided randomly into four groups: control, CP (20 mg/kg intraperitoneally), tempol (100 mg/kg/day, per os) + CP, and tempol only treatments. Blood samples were collected to analyze renal function parameters. Immunoblotting and immunohistochemical analysis were used to assess the level and localization of inflammatory markers. Tempol afforded protection to animals from CP-induced elevation of inflammatory markers as indicated by reduced expression of nuclear factor-kappa B, cyclooxygenase-2, and tumor necrosis factor-α in kidney tissue. Histological findings and analysis of kidney function markers corroborated with these findings confirming a nephroprotective role for tempol. In conclusion, this study provides important evidence for the promising anti-inflammatory effects of tempol which appears to contribute significantly to its nephroprotective action.

Potential Effect of β-casomorphin-7 on Lymphocyte and TLR\NF-κB Signaling Pathway in Intestinal Mucosa of Aged Mice

2020 ◽  
Author(s):  
Hong Yin ◽  
Xiaqing Su ◽  
Jijie Liu ◽  
Lihua Li ◽  
Lihua Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intestinal Mucosa ◽  
The Elderly ◽  
Potential Effect ◽  
Protective Role ◽  
Control Group ◽  
Relative Expression ◽  
Aged Mice ◽  
Histopathological Studies

The effect of â-Casomorphin-7 on intestinal mucosal immunity was investigated in aged mice. Mice were treated without or with different doses of â-Casomorphin-7 for 30 days. All mice were sacrificed and intestinal mucosa samples collection at the end of the experiment. Histopathological studies showed the tissue protective role of â-Casomorphin-7 in aged mice. The number of duodenal and jejunal epithelial lymphocytes decreased significantly Pandlt;0.05 The doses of duodenal and jejunal epithelial lymphocytes in mice were significantly Pandlt;0.05 increased in each dose group. The relative expression of TLR4,TRAF6 and NF-êB in the intestinal mucosa of the elderly model group was lower than that of the young control group. The low and middle dose groups significantly Pandlt;0.05 up-regulated the relative expression of TLR4, TRAF6 and NF-êB.The results suggest that â-Casomorphin-7 can improved intestinal mucosal immune decline likely through balancing TLR4\NF-êB signaling pathway.

scholarly journals Research Progress on the Role of Inflammatory Mechanisms in the Development of Postoperative Cognitive Dysfunction

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiao-xiang Tan ◽  
Li-Li Qiu ◽  
Jie Sun
Keyword(s):  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
The Elderly ◽  
Research Progress ◽  
Specific Mechanism ◽  
Related Factors ◽  
Synaptic Loss ◽  
Personality Changes ◽  
The Common

Postoperative cognitive dysfunction (POCD), as one of the common postoperative complications, mainly occurs after surgery and anesthesia, especially in the elderly. It refers to cognitive function changes such as decreased learning and memory ability and inability to concentrate. In severe cases, there could be personality changes and a decline in social behavior. At present, a great deal of research had been carried out on POCD, but its specific mechanism remains unclear. The release of peripheral inflammation-related factors, the degradation and destruction of the blood-brain barrier, the occurrence of central inflammation, and the neuronal apoptosis and synaptic loss could be promoted by neuroinflammation indicating that inflammatory mechanisms may play key roles in the occurrence of POCD.

miR-124-3p Ameliorates Isoflurane-Induced Learning and Memory Impairment via Targeting STAT3 and Inhibiting Neuroinflammation

2021 ◽  
pp. 1-7
Author(s):  
Fenghua Liu ◽  
Fengyu Qiu ◽  
Huayong Chen
Keyword(s):  
Learning And Memory ◽  
Memory Impairment ◽  
Potential Role ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spatial Learning And Memory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Dual Luciferase Reporter Assay

<b><i>Introduction:</i></b> Substantial evidence has indicated that isoflurane leads to learning and memory impairment. This study was designed to investigate the potential role of microRNA-124-3p (miR-124-3p) in isoflurane-induced learning and memory impairment in rats. <b><i>Methods:</i></b> Spatial learning and memory of rats were estimated by the Morris water maze (MWM) test after the construction of isoflurane-treated models. qRT-PCR was performed to assess the expression levels of miR-124-3p. The levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampal tissues were determined by enzyme-linked immunosorbent assay. The luciferase activity was determined by using a dual-luciferase reporter assay system. <b><i>Results:</i></b> The higher escape latency and lower time spent in the original quadrant were shown in isoflurane-treated rats compared with the control rats. Moreover, treatment with isoflurane could induce neuroinflammation, and miR-124-3p was poorly expressed in the hippocampal tissue of isoflurane-treated rats. Furthermore, STAT3 is a functional target of miR-124-3p, and inflammatory cytokine level was downregulated by miR-124-3p. <b><i>Discussion/Conclusion:</i></b> Combining the results of the current study demonstrates that miR-124-3p may have pivotal roles in improving isoflurane-induced learning and memory impairment via targeting STAT3 and inhibiting neuroinflammation.

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